Pheochromocytoma: The Basics

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What are pheochromocytomas?

Pheochromocytomas are very rare tumors of chromaffin cells, which are cells of the adrenal gland that make hormones called catecholamines. In pheochromocytoma, the cells overproduce catchecholamines, specifically norpinephrine, epinephrine (also known as adrenaline), and dopamine, all of which are necessary for our bodies to function. Pheochromocytomas are found in the adrenal glands; humans have two adrenals, and each sits on top of a kidney. Generally, only one adrenal gland, not both, is affected by a pheochromocytoma, but there may be multiple tumors in that gland.

Tumors that are found outside the adrenal glands (less than 10% of cases) are known as extra-adrenal pheochromocytomas or paragangliomas. Most tumors that start in the chromaffin cells do not spread to other parts of the body and are not cancer, but are benign tumors. A small percent of pheochromocytomas are malignant (cancerous); these are tumors that have spread outside the adrenal gland. Somewhere between 3 and 13% of pheochromocytomas are malignant.

What are the symptoms of pheochromocytomas?

Due to the presence of extra catecholamines that are produced by pheochromocytomas, patients may have hypertension (high blood pressure), which can cause headaches, as well as sweating, pounding of the heart, chest pain, and anxiety. These symptoms may occur in "episodes", with periods of time where there are no symptoms, but can also be persistent, depending on how the tumor is causing catecholamines to be released.

Am I at risk for pheochromocytoma?

The incidence of pheochromocytoma is 2 to 8 per million persons per year, making this a very rare tumor. Pheochromocyomas occur in less than 0.2 percent of patients with hypertension. Although pheochromocytomas may occur at any age, they are most common in people in their 30s to 40s and are equally likely to occur in men and women. About 10% occur in children. People with a rare genetic syndrome called multiple endocrine neoplasia (MEN) are at increased risk of pheochromocytoma, in addition to other tumors of endocrine glands, such as the thyroid. People with MEN are also more likely to have bilateral pheochromocytomas than those with sporadic (i.e. not related to a genetic syndrome) pheochromocytoma.

What are the signs of pheochromocytoma?

Pheochromocytomas are known for a classic group of symptoms: episodic headaches (headaches that occur over a period of time, followed by a period of time without headache, before returning again), sweating, and tachycardia (fast heart beat). However, most people with pheochromocytoma do not have all three of these symptoms and only half have at least one of these symptoms. The most common finding is hypertension, which lasts for short periods of time and may actually be normal in between elevated episodes. Keep in mind that the vast majority of patients with hypertension do not have pheochromocytoma.

How is pheochromocytoma diagnosed?

It has been reported that in somewhere between 10 and 50% of patients, the tumor is discovered incidentally, meaning it was found during a CT or MRI of the abdomen that was performed for an unrelated reason. In those patients who do have symptoms, there areblood and urine tests to measure the level of catecholamines in the body; these tests include 24-hour urinary catecholamines, vanillylmandelic acid, metanephrines and plasma metanephrines. These are all substances that are formed as catecholamines are broken down by the body and are therefore elevated in cases of pheochromocytoma.

As far as imaging tests are concerned, CT and MRI scans are most often used to detect the tumor. A special nuclear medicine scan called a meta-iodo-benzylguanidine (MIBG) scan may be used in cases where the laboratory tests or symptoms point to a pheochromocytoma, but none is found on CT or MRI. This test uses a radioactive form of iodine, which is attached to the MIBG molecule; MIBG is structurally similar to noradrenaline. This compound is given through a vein and the patient returns to the nuclear medicine department the following day for the actual scan. This delay allows the MIBG compound to concentrate in any tumor cells. The radioactive part of the compound allows these areas of tumor to be visualized on the scan. In addition, PET scanning is being studied in the diagnosis of these tumors.

How is pheochromocytoma staged?

There is no standard staging system for pheochromocytomas as there are for most types of cancer. Your team may refer to the cancer as localized (confined to one area; these are typically benign tumors), regional (spread to surrounding areas) or metastatic (spread to areas away from the original tumor).

Surgical Treatment

Once a pheochromocytoma is diagnosed, the treatment of choice is surgical resection, whether or not the tumor is benign or malignant. Surgical removal usually resolves any symptoms the patient was experiencing, including hypertension. Medical therapy is needed to manage the hypertension prior to surgery to prevent any complications of hypertension during the surgery. Because of the possibility of fluctuating catecholamine levels during the surgery, it is a risky procedure if not done with an experienced surgeon and anesthesiologist. A few weeks post-operatively, "plasma free metanephrines" (a laboratory test) are measured and if the results are normal, the resection is deemed complete.

Surgical resection can be curative in cases of localized pheochromocytoma. These tumors may metastasize (spread) to the lung, brain and bone. If it occurs, metastatic disease tends to progress slowly over a period of many years, though there can be ongoing complications related to the elevated catecholamine levels.

Other Treatments

Non-surgical treatments are used in patients who have unresectable, malignant or recurrent pheochromocytoma.

Previously, MIBG was discussed as a diagnostic tool, but for patients with malignant disease, MIBG may also be used as a treatment. Diagnostic MIBG scans usually use iodine-123, which decays (becomes inactive) faster than iondine-131 and is used as a treatment. To explain, MIBG, when given in a low dose, concentrates in areas of tumor, causing it to "light up" on a diagnostic scan. In higher doses, using iodine-131 MIBG, the radioactive iodine kills the cells that take up the MIBG. The treatment process involves an IV infusion of MIBG over a period of approximately 1 hour. Because radiation is emitted during and after the treatment, patients must stay within a designated area for a few days, until radiation levels in the body have dropped to the point where it is safe to leave. The treatment is well tolerated, but it can suppress the production of blood cells by the bone marrow, therefore blood counts will need to be checked. Follow-up after treatment may include repeating a diagnostic MIBG scan; ideally, if the treatment was successful there will be decreased MIBG uptake on the scan. While MIBG treatment can be very effective, there are some malignant pheochromocytomas, which do not take up MIBG, and in these tumors, I131-MIBG therapy will not work.

External beam radiotherapy is generally reserved for patients who have malignant (metastatic) pheochromocytoma with spread to the bone. The goal of radiotherapy in such situations is to relieve symptoms, such as pain. The dose and duration of treatment will vary according to the treatment site and other patient factors, but a two-week course is common.

Chemotherapy is also an option for treatment of symptomatic malignant pheochromocytoma, which has not responded to MIBG therapy. In a small study from the National Institute of Health (NIH), 18 patients were treated in a trial of a combination of three drugs: cyclophosphamide, vincristine, and dacarbazine, 72% had a biochemical response (measured as a decrease in catecholamine levels). The average length of response to treatment was 20 months. Similar to pre-surgical medical management, patients being treated with chemotherapy need to have their hypertension managed beforehand since chemotherapy can cause catecholamine release during treatment.

Finally, newer treatments, including molecular targeted therapies, such as sunitinib, are being studied in patients with malignant pheochromocytoma.